To investigate the role of the T-box gene Tbx3 in the human
developmental disorder ulnar-mammary syndrome (UMS), which is caused by
spontaneous mutations in TBX3, Virginia Papaioannou and colleagues
created Tbx3-knockout mice. They report, on
p. 2263, that although
heterozygous mutant mice have only a mild developmental phenotype – UMS
is a dominant disorder – the homozygous mutants recapitulate two of the
main features of the disorder: abnormal forelimb and mammary gland
development. Moreover, massive cell death of the yolk sac endoderm occurs in
Tbx3-null embryos at various times in midgestation. Subsequently, and
possibly as a result, mutant embryos die over several days, with none
surviving to birth. These mutant mice therefore reveal a novel role for Tbx3
in the yolk sac and provide a means for investigating the role of this gene in
limb and mammary gland development.

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